4-[(Z)-(4-bromophenyl)(ethoxyimino)methyl]-1′-[(2,4-dimethyl-1-oxido-3-pyridinyl)carbonyl]-4′-methyl-1,4′-bipiperidine (Formula I) is disclosed in pending, commonly-owned U.S. patent application Ser. No. 60/329,566, filed Oct. 15, 2001. 
The compound of Formula I is also disclosed in the commonly owned U.S. patent application Ser. No. 09/562,815, filed May 1, 2000, the disclosure of which is incorporated herein by reference. That provisional patent application discloses several novel antagonists of the CCR5 receptor which are useful for the treatment of AIDS and related HIV infections. CCR-5 receptors have also been reported to mediate cell transfer in inflammatory diseases such as arthritis, rheumatoid arthritis, atopic dermatitis, psoriasis, asthma and allergies, and inhibitors of such receptors are expected to be useful in the treatment of such diseases, and in the treatment of other inflammatory diseases or conditions such as inflammatory bowel disease, multiple sclerosis, solid organ transplant rejection and graft v. host disease.
Generally, pharmaceutical compounds are used as their pharmaceutically acceptable salts. This is also true of CCR5 receptor antagonists such as the compound of Formula I, which makes the preparation of pharmaceutically acceptable salts of such compounds quite important.
The compound of Formula I has no chiral centers and the geometry of the oxime is controlled as the Z configuration by the chemical synthesis. However, the compound of Formula I exists as a mixture of rotational isomers or rotamers due to the restricted rotation about the two single bonds, marked a and b in FIG. 1. The relative relationship between the four rotamers is depicted in Scheme 1. As such Structures A and B have a diastereomeric relationship and Structures C and D have a diastereomeric relationship. For convenience, the four rotamers are denoted as isomers 1, 2, 3 and 4, in order of their elution from a chiral HPLC column.
While general synthetic approaches for salts typically yield a 1:1:1:1 ratio of the rotamers 1, 2, 3 and 4, it would be preferable to find methods of synthesis that would yield rotamer populations that are enriched in certain rotamers preferentially.